Pulmonary delivery of nicotine using the AERx System

DESCRIPTION (provided by applicant): Each year more Americans die from smoking-related diseases than from alcohol, AIDS, drug abuse, car accidents, fire, suicide and murder-combined. Smoking costs the United States approximately $97.2 billion each year in healthcare costs and lost productivity. Currently 20% of the US population, or 50 million people, smoke or use tobacco products. Of these, up to 20 million will quit for at least a day with only 10% of these remaining tobacco free one year later. This equates to only 2-3% of smokers successfully quitting each year, with quitting defined as smoke free for 1 year. Strategies to achieve smoking cessation include nicotine replacement therapies (NRT), non-nicotine replacement therapies, community cessation programs and advice from health care providers. All of the NRTs have different levels of efficiency and variable rates of nicotine absorption. While each system is a valuable aid in smoking cessation, absolute success rates are low. Development of new systems is critical in an effort to both bypass limitations of existing systems and to provide options for matching smokers to treatment. The objective of this proposal is to evaluate the feasibility of delivery of aerosolized nicotine via inhalation using the AERx Pulmonary Delivery System. The lung represents an attractive target for nicotine delivery and would allow achievement of pharmacokinetic profiles similar to nicotine derived from cigarette smoke, which could impact compliance and success rates. Benefits of an inhaled AERx-nicotine product would include higher nicotine replacement levels, fast onset of action, simulation to cigarette smoking, low inter-intrasubject variability and programmed dose reduction capabilities. The AERx System has successfully delivered a variety of molecules in clinical trials and has broad applications to deliver a wide range of molecules (from small molecules to proteins and nucleic acids). The Phase I research plan will include nicotine formulation and assay development, optimization of aerosol performance, evaluation of formulation compatibility with materials used in the AERx System, development of dose-titration capabilities. The long-term goal of this proposed project is to develop an inhalation product (the AERx-nicotine) as a therapy for smoking cessation.